CN110302296A

CN110302296A - A kind of Chinese medicine composition and its preparation method and application for treating liver-stomach disharmony or/and pharyngeal discomfort

Info

Publication number: CN110302296A
Application number: CN201910464507.5A
Authority: CN
Inventors: 周立
Original assignee: Teaching Hospital of Chengdu University of TCM
Current assignee: Teaching Hospital of Chengdu University of TCM
Priority date: 2019-05-30
Filing date: 2019-05-30
Publication date: 2019-10-08
Anticipated expiration: 2039-05-30
Also published as: CN110302296B

Abstract

The invention discloses a kind of Chinese medicine compositions for treating liver-stomach disharmony or/and pharyngeal discomfort, it is prepared by the raw material of following weight proportion: 7-13 parts of radix bupleuri, 7-13 parts of rhizoma cyperi, 7-13 parts of dried orange peel, 7-13 parts of rhizoma pinellinae praeparata, 7-13 parts of Cortex Magnoliae Officinalis, 7-13 parts of perilla leaf, 4.2-7.8 parts of the coptis, 7-13 parts of myrobalan, 7-13 parts of blood clam, 10.5-19.5 parts of Radix Codonopsis, 7-13 parts of radix paeoniae rubra, 3.5-6.5 parts of Radix Glycyrrhizae.The traditional chinese medicine composition of the invention has liver-smoothing, qi-regulating, invigorating the spleen for eliminating dampness, the effect of pharynx-clearing throat-benefiting, and remarkable result is suitable for clinical promotion and application.

Description

A kind of Chinese medicine composition that treating liver-stomach disharmony or/and pharyngeal discomfort and its preparation side Method and purposes

Technical field

Present invention relates particularly to a kind of Chinese medicine compositions and preparation method thereof for treating liver-stomach disharmony or/and pharyngeal discomfort And purposes.

Background technique

Laryngopharyngeal reflux disease (LPRD) refers to that gastric content reflux, with upper bit, causes a series of to esophageal sphincter The general name of sings and symptoms.Clinical manifestation is bottleneck throat foreign body sensation, persistently hawks, trachyphonia, fatigue of voice, have sore throat, is chronic The symptoms such as cough, expiratory dyspnea, laryngospasm, asthma and vocal cords postcommissure region mucous membrane thicken, are plump, and vocal cords diffusivity is filled There are throats' signs such as granuloma, Hilton's sac's disappearance, subglottic stenosis in blood, oedema when serious, 10% hals,Nasen und Ohrenheilkunde is medical to suffer from There are reflux symptoms and sign in person.There are experimental research suggested high fat diet and chronic sleep deprivation, rat can be caused to occur LPRD。

Gastroesophageal reflux disease (gastroesophageal reflux disease, GERD) refers to Stomach duodenum A series of symptoms caused by content reflux to oesophagus, such as cusalgia after sour regurgitation, burn feeling, breastbone.Some researches show that be diagnosed as The patient of gastroesophageal reflux disease is often with a lot of other symptoms, wherein having 72% to show with sphagitis.The past ear-nose-throat department Doctor has part doctor that gastroesophageal reflux disease and Laryngopharyngeal reflux disease are lumped together, Koufman when seeing and treating patients patient Report LPRD not only deposits difference with gastroesophageal reflux disease on sings and symptoms for the first time, also variant on pathologic, physiologic.

" Laryngopharyngeal reflux disease diagnosis and therapy Consensus of experts (2015) " suggest that at least carrying out 8 weeks tentative controls It treats, responder can diagnose after 8 weeks.LPR includes acid reflux and alkaline reflux, and PPI is invalid to non-acid reflux.Long-term clothes With PPI be likely to occur headache, diarrhea, appetite stimulator, the nervous system disease, arrhythmia cordis, endocrine system, influence vitamin and Mineral metabolism influences a series of side effects such as iron absorption, anaemia.Though PPI class drug is the effective drug of accepted treatment, lead to It crosses and consults domestic and international pertinent literature discovery, using the curative effect of PPI treatment in different therapeutic doses, times for spraying and treatment cycle etc. The result of study of aspect is also not quite similar.So apparently with regard to current result of study, the treatment standard and reasonability of PPI treatment are all Remain dispute.

Summary of the invention

To solve the above problems, the present invention provides a kind of Chinese traditional medicine compositions for treating liver-stomach disharmony or/and pharyngeal discomfort Object, it is prepared by the bulk pharmaceutical chemicals of following weight proportion:

7-13 parts of radix bupleuri, 7-13 parts of rhizoma cyperi, 7-13 parts of dried orange peel, 7-13 parts of rhizoma pinellinae praeparata, 7-13 parts of Cortex Magnoliae Officinalis, perilla leaf 7-13 Part, 4.2-7.8 parts of the coptis, 7-13 parts of myrobalan, 7-13 parts of blood clam, 10.5-19.5 parts of Radix Codonopsis, 7-13 parts of radix paeoniae rubra, Radix Glycyrrhizae 3.5- 6.5 part.

Further, it is prepared by the bulk pharmaceutical chemicals of following weight proportion:

10 parts of radix bupleuri, 10 parts of dried orange peel, 10 parts of rhizoma pinellinae praeparata, 10 parts of Cortex Magnoliae Officinalis, 10 parts of perilla leaf, 6 parts of the coptis, is scolded at 10 parts of rhizoma cyperi Sub 10 parts, 10 parts of blood clam, 15 parts of Radix Codonopsis, 10 parts of radix paeoniae rubra, 5 parts of Radix Glycyrrhizae.

Further, it is active constituent that it, which is by the medicinal powder of bulk pharmaceutical chemicals or the water of bulk pharmaceutical chemicals or extractive with organic solvent, is added The preparation that upper pharmaceutically acceptable auxiliary material is prepared.

Further, the preparation is oral preparation.

Further, the oral preparation be powder, paste, granule, tablet, capsule, oral solution or dripping pill, it is excellent Select granule.

The present invention also provides a kind of preparation method of aforementioned Chinese medicine composition, it the following steps are included:

(1) bulk pharmaceutical chemicals are weighed according to the proportion；

(2) bulk pharmaceutical chemicals grind water or organic solvent extracting solution for powder or bulk pharmaceutical chemicals, be added pharmaceutically common auxiliary material or Complementary ingredient to get.

The present invention also provides a kind of aforementioned Chinese medicine compositions in the drug for preparing dispersing stagnated hepatoqi and/or normalizing the stomach by guiding QI downward Purposes.

The present invention also provides a kind of aforementioned Chinese medicine compositions in preparation treatment pectoralgia, heartburn and/or stomachache drug Purposes.

The present invention finally provides a kind of purposes of aforementioned Chinese medicine composition in the drug of preparation treatment pharyngeal discomfort.

Further, the pharyngeal discomfort be persistently hawk, foreign body in pharynx sense, abundant expectoration and/or nasal mucus flow backwards.

In the traditional chinese medicine composition of the invention, radix bupleuri enters liver and gallbladder warp, and property, which rises, to be dissipated, key medicine of the successive dynasties as treatment irritability stasis, Kind soothing liver-qi stagnation, surname dissipate is thoroughly evil, therefore is monarch drug in a prescription.Rhizoma cyperi enters Liver Channel and kind soothing liver-qi stagnation, regulating qi-flowing for relieving pain, shares total solution with radix bupleuri The benefits of Liver Channel stasis, enhancing promoting qi circulation and relieving pain；Rhizoma pinellinae praeparata, returns spleen stomach meridian, the suitable stomach function regulating of function, eliminating dampness and eliminating phlegm, stopping nausea and vomiting by lowering the adverse flow of QI；It is altogether minister Medicine.Dried orange peel, returns spleen stomach meridian is eliminating dampness and eliminating phlegm in function benefaction controlled atmosphere for the key medicine for controlling the taste stagnation of the circulation of vital energy；Cortex Magnoliae Officinalis, returns spleen stomach meridian, function Eliminating dampness dissolving phlegm, lower gas removes full mutually must be used with rhizoma pinellinae praeparata, dried orange peel, eliminating dampness except full in promoting the circulation of qi tune；Perilla leaf, returns spleen stomach meridian, promoting the circulation of qi In width, de-swelling, anti-vomiting in energy width；The coptis, it is bitter, it trembles with fear, returns spleen stomach meridian, heat-clearing and damp-drying drug, purging fire for removing toxin, for the strongly fragrant middle coke of heat Feeling of fullness, vomiting, acid regurgitation；Myrobalan, function are apt to throat and open sound；Blood clam, hyperacidity and pain relief cure mainly epigastric pain, acid regurgitation；Radix Codonopsis, returns spleen Through, it is drying damp and strengthening spleen, it is the first key medicine of invigorating the spleen, "Nei Jing" " is shown in the disease of liver, knowing the liver disease will be transmitted into the spleen, in the ban real spleen ", therefore sees that the disease of liver cannot Liver is only controlled, cares for shield spleen in the ban；Radix paeoniae rubra enters Liver Channel, because of " pathogen usually intruding into collateral in protracted disease ", therefore for promoting blood circulation and removing obstruction in channels, and can rise priming enter Liver Channel it Effect, is altogether adjutant.Radix Glycyrrhizae enters spleen, stomach meridian, reconciles all medications, and serving as makes medicine.Said medicine compatible use has liver reason of relaxing Gas, invigorating the spleen for eliminating dampness, the effect of pharynx-clearing throat-benefiting have remarkable result in terms for the treatment of liver-stomach disharmony and pharyngeal discomfort, are suitable for clinic It promotes the use of.

Tests prove that: soothing liver and harmonizing stomach medicine composite for curing Laryngopharyngeal reflux disease (syndrome of incoordination between liver and stomach) of the present invention have compared with Good clinical efficacy.Be obviously improved patient's foreign body sensation in the throat, hawk, abundant expectoration or nasal mucus flow backwards, it is heartburn stomachache etc. main clinic symptoms.

Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.

The specific embodiment of form by the following examples remakes further specifically above content of the invention It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention The technology realized all belongs to the scope of the present invention.

Detailed description of the invention

1 Technology Roadmap of Fig. 1 test example

1 effect analysis figure of Fig. 2 test example

2 Technology Roadmap of Fig. 3 test example

2 effect analysis figure of Fig. 4 test example

Specific embodiment

The preparation of embodiment 1, drug of the present invention

Formula: radix bupleuri 10g, rhizoma cyperi 10g, dried orange peel 10g, rhizoma pinellinae praeparata 10g, Cortex Magnoliae Officinalis 10g, perilla leaf 10g, coptis 6g, myrobalan 10g, blood clam 10g, Radix Codonopsis 15g, radix paeoniae rubra 10g, Radix Glycyrrhizae 5g.

Preparation method: weighing each raw material by formula, crushes, and is sieved, and mixing is added water to cook, is concentrated, drying and be granulation into particle Agent, total 116g.

Application method: one time 38.7g/ times, three times per day, 100ml warm boiled water, half an hour warmly takes after meal.

The preparation of embodiment 2, drug of the present invention

Formula: radix bupleuri 7g, rhizoma cyperi 7g, dried orange peel 7g, rhizoma pinellinae praeparata 7g, Cortex Magnoliae Officinalis 7g, perilla leaf 7g, coptis 4.2g, myrobalan 7g, watt Stupefied sub- 7g, Radix Codonopsis 10.5g, radix paeoniae rubra 7g, Radix Glycyrrhizae 3.5g.

Preparation method: weighing each raw material by formula, crushes, and is sieved, and mixing is added water to cook, is concentrated, drying and be granulation into particle Agent.

The preparation of embodiment 3, drug of the present invention

Formula: radix bupleuri 13g, rhizoma cyperi 13g, dried orange peel 13g, rhizoma pinellinae praeparata 13g, Cortex Magnoliae Officinalis 13g, perilla leaf 13g, coptis 7.8g are scolded Sub- 13g, blood clam 13g, Radix Codonopsis 19.5g, radix paeoniae rubra 13g, Radix Glycyrrhizae 6.5g.

Illustrate beneficial effects of the present invention below by way of test example:

Test example 1:

Research purpose

Domestic and international more and more doctors begin to focus on Laryngopharyngeal reflux disease, still have not for the Clinics and Practices of this disease It is few to query.Proton pump inhibitor is this main processing means of disease of western medical treatment, but it is there are gastrointestinal discomfort and long-term use is deposited Causing the danger such as myocardial damage, senile fracture, the theoretical method based on tcm treatment according to syndrome differentiation, more and more Chinese medicine scholars Laryngopharyngeal reflux disease is treated with Chinese medicinal formulae in conjunction with itself clinical experience, but traditional Chinese medicine is more scattered to the discussion of this disease, no Enough systematizations theorize.This research is inverse using dispersing stagnated hepatoqi, drop by according to the clinical testing procedure of single-blind randomized parallel control Stomach function regulating method is to treat Laryngopharyngeal reflux disease (syndrome of incoordination between liver and stomach) patient from quasi- Chinese medicine compound prescription.To be expected that by examining The improvement situation for controlling Patients Before And After sign and symptom compares and analyzes, and probes into soothing liver and harmonizing stomach ruling by law and treats reflux pharyngolaryngitis Clinical value, thus advantage of the clear traditional Chinese medicine in treatment Laryngopharyngeal reflux disease.To the depth of Laryngopharyngeal reflux disease theory Enter discussion and experimental study, help to seek the more effective diagnosis and treatment method of this disease, and valuable theoretical, practice reference is provided.

Research approach

1 experimental design

Using the clinical trial design method of single-blind randomized, placebo parallel control.By subject with the ratio of 1:1 with Machine is divided into test group and control group.

2 research objects

2.1 subject

All subjects of this research go to a doctor both from September, 2016 to 2 months 2017 periods in Chengdu University of Traditional Chinese Medicine The patient of affiliated hospital's hals,Nasen und Ohrenheilkunde outpatient service, this clinical research is collected altogether meets patient 50 that LPRD is included in standard.

2.2 subject's diagnostic criteria

2.2.1 Western medicine diagnostic criteria

According to " Laryngopharyngeal reflux disease diagnosis and therapy Consensus of experts (2015) ", all equal references of LPRD suspected case Reflux symptom index scale (RSI), the reflux sign scale (RFS) of the formulations such as Belafsky are diagnosed.Divided with RSI > 13 And/or RFS > 7 is allocated as the diagnostic criteria of Laryngopharyngeal reflux disease.

2.2.2 Standards of Chinese Medical Syndrome Differentiation

Chinese medicine there is no this disease the diagnostic criteria of specification, and according to regular higher education National planning teaching material, " Chinese medicine is examined It is disconnected learn " and " new Chinese medicine guideline of clinical investigations " in about the TCM syndrome diagnostic criteria of syndrome of incoordination between liver and stomach determine LPRD Syndrome of incoordination between liver and stomach.

Primary symptom: gastral cavity side of body rib turgor or distending pain, acid regurgitation, belch, hiccup, veins string.

Minor symptom: depressed emotion, irritable, do not feel like eating, sighing frequently, gastric discomfort.

Meet the above primary symptom 3 or primary symptom 2 plus minor symptom 2, i.e., it is diagnosable.

It the selection of 2.3 subjects and exits

2.3.1 it is included in standard

1. meeting Laryngopharyngeal reflux disease Western medicine diagnostic criteria person；

2. meeting Chinese medicine syndrome of incoordination between liver and stomach CM syndrome differentiation criterion person；

3. the age between 18-65 one full year of life, male or female；

4. this experimenter of voluntary participation.

2.3.2 exclusion criteria

1. having taken other associated treatments measure person within January before this is medical；

2. the age is in under-18s or over-65s person；

3. in gestation, nursing period, or being in standby pregnant phase person；

4. the known constituent allergy sufferers to clinical test drug；

5. can not understand due to various reasons and complete the relative recordings persons such as case observation table as required；

6. participating in other drugs clinical test person；

7. suspection has alcohol, history of substance abuse person.

2.3.3 it rejects and the standard that falls off

1. further testing program person is changed in treatment or requirement to patient's refusal in research process；

2. there are adverse events or severe complication person occurring；

3. the drug person for having used other influences curative effect and tolerance to judge；

4. disobeying doctor's advice drug user；

5. actively exiting clinical test person；

6. not being included within curative effect statistics for the course for the treatment of less than 1/2.

2.3.4 fall off case management

1. should be assessed it because of the patient that adverse reaction falls off to confirm its appearance and using the related of drug Property, and suitable treatment recommendations are provided；

2. because treatment be in vain by due to the person of falling off, corresponding measure should be taken according to the actual situation；

3. should be appreciated that it exits reason for the patient for actively exiting treatment, and make respective record.

3 intervening measures

3.1 behavior intervention

After entering group, before carrying out trial drug and intervening and during experimental study, repeatedly to patient lifestyle and diet Habit carries out propaganda and education, and main contents include:

1. lifestyle modification

Avoid stress, depressive emotion, overworked；Appropriate exercise controls weight, is sure not acutely to transport after the meal or before sleeping It is dynamic；The factor for increasing intra-abdominal pressure is reduced, such as constipation, acutely coughs, be in tights, waistband tension；It takes and lies on the left side when sleep Position, and by bed head raising 15-20cm, etc..

2. eating habit intervention

It is appropriate to increase food consistency, it has more meals a day but less food at each, avoids satiating, first 3 hours taboo diet of going to bed；Avoid edible fried food Product, spicy food, high-fat foods；Avoid edible citrus fruit, cider, pumpkin, sweet potato, purple sweet potato, Yoghourt, catsup, dense The foods such as tea, chocolate, peppermint, garlic, soda；Avoid edible coffee and other food, drinks containing caffeine；It avoids It drinks and alcoholic drink；Recommend low sour diet, can suitably eat base-forming food etc..

3.2 trial drug

What test group gave being exempted from by Hospital Affiliated To Chengdu Traditional Chinese Medicine Univ decocting the preparation of granular preparation room has soothing liver and harmonizing stomach function The Chinese medicine compound prescription of energy is exempted to decoct particle (composition: radix bupleuri 10g, rhizoma cyperi 10g, dried orange peel 10g, rhizoma pinellinae praeparata 10g, Cortex Magnoliae Officinalis 10g, perilla leaf 10g, coptis 6g, myrobalan 10g, blood clam 10g, Radix Codonopsis 15g, radix paeoniae rubra 10g, Radix Glycyrrhizae 5g).Advise patient with the punching of 100ml warm water Clothes, half an hour warmly takes after meal, one-measure each time, three times per day, continuously takes 3 weeks.

3.3 placebo

Control group give being exempted from by Hospital Affiliated To Chengdu Traditional Chinese Medicine Univ decocting the preparation of granular preparation room outer packing, dosage form, The free decoction particle placebo identical with test group such as dosage, color, smell.Advise patient with 100ml warm boiled water, after meal Half an hour warmly takes, one-measure each time, three times per day, continuously takes 3 weeks.

4 observation index

4.1 overview indexs

1. basic document: name, gender, age, home address and contact method etc..

2. state of an illness data: main suit, past medical history, allergies, bad habit etc..

4.2 parameters for observation on effect

Subject fills in VAS and RSI scale before treatment, after treatment 1 week, after treatment 2 weeks, when treatment end.It grinds The person of studying carefully by strobolaryngoscope inspection result is filled in RFS scale before treatment, after treatment.

4.3 the standard of curative effect evaluation

Referring to " Laryngopharyngeal reflux disease diagnosis and therapy Consensus of experts (2015) ", symptom improvement degree is regarded after treatment Feel simulation point system (visual analogue scale, VAS) scoring, is made referring to " new Chinese medicine guideline of clinical investigations " Fixed following curative effect determinate standard:

Symptom improves percentage=(pre-treatment score-post treatment integral)/pre-treatment score × 100%

1. effective: symptom disappears substantially, RSI≤13 point；Symptom improves percentage >=80%；

2. effectively: symptom improves 50% or more, and RSI is reduced, but still > 13 divides；50%≤symptom improves percentage < 80%；

3. invalid: symptom is without improvement, and symptom improvement rate < 50%, RSI is without reduction.

4.4 safety evaluatios and standard

1 grade: safety, it is without any adverse reactions；

2 grades: there is adverse reaction, can continue to be administered without doing any processing in relatively safety；

3 grades: having safety issue, moderate adverse reaction occur, rationally can continue to be administered after processing；

4 grades: because adverse reaction stops to test.

4.5 Adverse Event

4.5.1 the extent of disease severity of adverse events

Slight: subject does not influence to treat, does not need specially treated still to endure, and restores subject also without influence.

Moderate: subject is difficult to endure, and needs specially treated, has a direct impact to the recovery of subject's state of an illness.

Severe: jeopardizing subject's life, can disable or even lethal, and rescue immediately is needed to handle.

4.5.2 the record of adverse events

Adverse events record sheet is filled in during test strictly according to the facts, when recording the time of origins of adverse events, severity, continuing Between, the effective measures taken and lapse to.

4.5.3 the first aid process of adverse events

If any adverse events occur during test, corresponding treatment should be taken immediately；In case of serious bad Event must then deactivate ongoing associated treatment measure immediately, and take effective treatment.

4.6 terminate to test ahead of time

1. sense of discomfort occurs during the test in patient, and is possible to influence life security, should stop immediately；

2. the therapeutic agent less effective that project uses does not have research observation meaning；

3. project, occurring great bias on conceptual design or during execution, drug effect evaluation is queried.

The estimation of 5 sample sizes

This test, chooses test group and control group, and drafting test is efficient comparison between two groups, according to prerun early period It tests and related literatures is consulted, test group effective percentage is 80% or so, and control group effective percentage is 35% or so, in order to improve this The power of test of secondary test estimates the sample content of two groups of carry out random sample designs.

Test stone: one-sided test is chosen；

Condition: the non-matching and case load case equal with control group: n=n1=n2；

Sample Size Calculation:

P=(P₁+P₂)/2；

Inspection parameter:

α: the significance of inspection takes 0.05, Z_α=1.645 (taking one-sided test)；

β: for the probability for making II class mistake, 0.10, i.e. power of test 1- β=0.90, Z are taken_β=1.282 (take unilateral inspection It tests)；

P₁: for test group effective percentage；P₁=80%；

P₂: for control group effective percentage；P₂=35%；

Calculated result: n=n1=n2=20 is obtained after being computed；

It is calculated through formula, when two groups of single group sample contents are 20, total Sample size has had inspection when being 40 Test efficiency.It is contemplated that might have the case that falls off in test, it is estimated as 10%-20%, therefore appropriate enlarged sample amount.To sum up, When practical population sample content is at 50 or so, systematic error can be reduced, guarantees that research conclusion has certain reliability.Together When can to avoid sample content it is very few caused by power of test it is relatively low false Yin/Yang and sample content it is excessive caused by The wasting of resources.

6 random devices and blind

6.1 random device

By the way of table of random number, be included in and the subject of exclusion criteria to meeting, with medical sequencing with Machine is divided into test group and control group.

The setting of 6.2 blind

This research is using mono blind method, i.e., during the test, patient does not know controlling between grouping information and different groups Treatment scheme, while researcher is not involved in the statistics of test data.

7 statistical methods

This applying topic SPSS22.0 is for statistical analysis to final data.Enumeration data is examined with χ 2；Metering Data carries out test of normality first, if two sample averages for meeting normal distribution compare using independent samples t test, with This relatively uses paired t-test before and after treatment, and data are usedExpression；Rank sum test is chosen in the comparison of rate between two groups；Regulation If P < 0.05, there is statistical significance.

8 technology paths

See Fig. 1

As a result

It is efficient between two groups after 1 treatment end of table to compare

By table 1 and Fig. 2 it is found that through rank sum test, after treatment is finished, test group P=0.001 compared with control group curative effect (P < 0.01), two groups of curative effects have significant difference.

Two groups of symptom scores compare after 2 treatment end of table

As shown in Table 2, through independent samples t test, after treatment end two groups persistently hawk, phlegm is excessive or nasal mucus is flow backwards, Foreign body sensation in the throat, the stomachache of heartburn pectoralgia, RSI, VAS score on relatively, and there are statistical difference (P < 0.05), have clinical meaning Justice.

Result of study: soothing liver and harmonizing stomach granule therapy Laryngopharyngeal reflux disease (syndrome of incoordination between liver and stomach) of the present invention has preferably clinical treat Effect.Research find said preparation can be obviously improved patient's foreign body sensation in the throat, hawk, abundant expectoration or nasal mucus are flow backwards, heartburn stomachache etc. is main Clinical symptoms.

Test example 2:

1 research purpose

Early-stage study according to single-blind randomized placebo clinical testing procedure, using dispersing stagnated hepatoqi, normalizing the stomach by guiding QI downward method To be treated from quasi- Chinese medicine compound prescription to Laryngopharyngeal reflux disease (syndrome of incoordination between liver and stomach) patient, curative effect up to 78.26%, therefore this The secondary clinical testing procedure continued using Single-blind randomized control, to be expected that by the improvement to diagnosis and treatment Patients Before And After sign and symptom Situation compares and analyzes, and the clinical value that reflux pharyngolaryngitis is treated in soothing liver and harmonizing stomach ruling by law is probed into, so that clear traditional Chinese medicine exists Treat the advantage in Laryngopharyngeal reflux disease.Further investigated and experimental study to Laryngopharyngeal reflux disease theory, help to seek The more effective diagnosis and treatment method of this disease is sought, and valuable theoretical, practice reference is provided.

2 research objects

2.1 subject sources

Met to 2 months 2018 in Hospital Affiliated To Chengdu Traditional Chinese Medicine Univ ear-nose-throat department outpatient service from May, 2017 and receives Enter 52 patients of standard.

2.2 diagnostic criteria

2.2.1 Western medicine diagnostic criteria

According to " Laryngopharyngeal reflux disease diagnosis and therapy Consensus of experts (2015) ", all equal references of LPRD suspected case Reflux symptom index scale (RSI), the reflux sign scale (RF S) of the formulations such as Belafsky are diagnosed.Divided with RSI > 13 And/or RFS > 7 is allocated as making a definite diagnosis standard for LPRD.

2.2.2 Standards of Chinese Medical Syndrome Differentiation

The above primary symptom 3 or primary symptom 2 plus minor symptom 2, i.e., it is diagnosable.

2.3 subjects are included in standard:

2. reaching the Standards of Chinese Medical Syndrome Differentiation person of syndrome of incoordination between liver and stomach type；

3. the age between 18-65 one full year of life, male or female；

4. this experimenter of voluntary participation.

2.4 Subject Exclusion Criterias:

2. the age is in under-18s or over-65s；

3. in gestation, nursing period, or being in standby pregnant phase person；

4. the infull person of Liver and kidney function；

5. allergic constitution or the known constituent allergy sufferers to clinical test drug；

6. can not understand due to various reasons and complete the relative recordings persons such as case observation table as required；

7. participating in other drugs clinical test person；

8. alcohol, history of substance abuse person can be suspected to have.

Note: it is all to meet above-mentioned any one patient, that is, it should give exclusion.

2.5 subjects fall off, reject and the standard of termination test

1. all cases for not meeting the standard of being included in and being strayed into should give exclusion；

2. there are adverse events or severe complication person occurring；

4. disobeying doctor's advice drug user；

5. actively exiting clinical test person；

6. further testing program person is changed in treatment or requirement to patient's refusal in research process；

7. being greater than 1/2 for the course for the treatment of, should be included within curative effect statistics.

2.6 fall off case management

3 research approaches

3.1 experimental design

Subject is included in test group and control group in 1:1 ratio using random, single blind check experiment by this experiment at random.

3.2 sample content

52 patients are included in this test altogether, wherein test group 26, and control group 26.

3.3 random devices and blind

3.3.1 random device

It by the way of table of random number, is included in and the subject of exclusion criteria to meeting, medical successive of group basis Sequence is randomly assigned.

3.3.2 random device is implemented

Specific method is: carrying out completely random grouping with SAS9.0, elder generation is defeated from 1-200 the serial number for being included in patient in advance Enter in it, then generate random number, random number is ranked up, organizing quantity according to the observation is 2, it is randomly divided into 1,2 two group, Generate the sequence being randomly assigned.Take envelope method to being hidden at random.First according to sequencing to sealing, lighttight letter Envelope is encoded.And sequence is randomly assigned with being sequentially loaded into closed lighttight envelope.Then qualified subject is allowed face to face It successively opens an envelope, is included in 1 group or 2 groups according to sequence.All subjects are included in test group and control group by random effect, and every group It is stringent to be treated according to experiment process.52 patients being actually included in are included in observation group and control group according to this law at random, often Group 26.

3.3.3 blind is set

The MAIN OUTCOME MEASURES of this research is VAS grade form and RSI scale and RFS scale, Analysisof Self-rating Anxiety Scale (SAS), Larger by subjective impact, due to subject study personnel are limited etc., therefore this test uses single blind study, i.e., in test process In, researcher knows the grouping situation and therapeutic scheme of patient, but patient is not allowed to know grouping situation and different groups as far as possible Between treatment measures.

3.4 testing equipment

3.4.1 strobolaryngoscope

Strobolaryngoscope system includes full digital wosap tv system, DIVAS video editing and analysis software (Germany XION company).System uses electronic stroboscopic mode, full digital processing and transmission data.Subject takes seat when inspection, and intranasal is inserted Enter laryngoscope, sufficiently expose cavum laryngis, observation patient's glottis is upper and lower and surrounding structure, and computer is with the speed of 25 frame images of capture per second Degree, which is recorded, checks overall process, is then played back, is analyzed, diagnosed and image prints.

3.4.2 Voice acoustics analysis

Test equipment uses Germany's XION company DiVAS voice analysis software, and the voice parameter that when analysis is related to mainly has: Fundamental frequency and frequency range.Subject practices comfortable steady hair long vowel/a first :/for several times, sound microphone will be adopted after skillfully stablizing It is placed at the 15cm of patient's lip center, is biased to left side bicker.Tone and the loudness hair that subject is comfortably accustomed to oneself/ A :/3 times, every time for about 7s or so.Comfort conditions after patient's depth air-breathing are advised to issue long/a later :/, and when continuing longest Between, while record sound sample.Above two measurement carries out 3 times respectively.Using DiVAS voice analysis software analysis sound sample: in middle part Steady section takes 3s or so length sound sample to carry out fundamental frequency and frequency range measurement.

The selection of 3.5 trial drugs

Early period, placebo was researches show that this compound is effective for treatment liver-stomach disharmony type Laryngopharyngeal reflux disease, and PPI class Drug is the effective therapeutic agent generally acknowledged in world wide, and lansoprazole tablet is as PPI class drug, and moderate, purchase is convenient, Therefore select it as control drug.

3.6 intervening measure

3.6.1 behavior intervention

Lifestyle modification

Avoid stress, depressive emotion, overworked；Appropriate exercise controls weight, is sure not acutely to transport after the meal or before sleeping It is dynamic；Reducing makes the factor that increases in abdomen, such as constipation, acutely coughs, is in tights, waistband tension, bend over after the meal, remove weight； Take left lateral position when sleep, and by bed head raising 15-20cm etc..

Eating habit intervention

3.6.2 trial drug

Give the Chinese medicine compound prescription with soothing liver and harmonizing stomach function for being exempted to decoct the preparation of granular preparation room by Chengdu University of Traditional Chinese Medicine Grain (composition: radix bupleuri 10g, rhizoma cyperi 10g, dried orange peel 10g, rhizoma pinellinae praeparata 10g, Cortex Magnoliae Officinalis 10g, perilla leaf 10g, coptis 6g, myrobalan 10g, watt Stupefied sub- 10g, Radix Codonopsis 15g, radix paeoniae rubra 10g, Radix Glycyrrhizae 5g).Advise patient with 100ml warm boiled water, half an hour warmly takes after meal, and 1 time 1 Lattice are continuously taken 3 weeks three times a day.

3.6.3 positive control medicine

Give lansoprazole tablet (Jiangsu Yangtze River medicine company, specification 15mg/ piece) 15mg, it is 1 day 2 times, empty from morning and before dinner Abdomen is taken, and treatment 3 weeks as a treatment course.

3.7 observation index

3.7.1 overview index

Basic document: name, gender, age, home address and contact method etc..

State of an illness data: main suit, past medical history, allergies, bad habit etc..

3.7.2 parameters for observation on effect

Subject fills in VAS, SAS and RSI amount before treatment, after treatment 1 week, after treatment 2 weeks, after treatment 3 weeks Table, researcher passes through before treatment, after treatment to be filled in RFS scale by strobolaryngoscope inspection result and carries out vocal acoustics point Analysis obtains base frequency range.

3.7.3 therapeutic evaluation

Final main indicator is that symptom improves percentage.

It is regarded referring to symptom improvement degree after " Laryngopharyngeal reflux disease diagnosis and therapy Consensus of experts (2015) " treatment Simulation point system (visual analogue scale, VAS) scoring is felt, since VAS scores no quantization classification, referring to " Chinese medicine Clinical Researches of New Drugs guideline " formulate following curative effect determinate standard:

Symptom improves percentage=(pre-treatment score-post treatment integral)/pre-treatment score * 100%

Effective: symptom disappears substantially, RSI≤13 point；Symptom improves percentage >=80%；

Effective: symptom improves 50% or more, and RSI is reduced, but still > 13 divides；50%≤symptom improves percentage < 80%；

Invalid: symptom is without improvement, and symptom improvement rate < 50%, RSI is without reduction.

3.7.4 safety evaluatio and standard

1 grade: safety, it is without any adverse reactions；

4 grades: because adverse reaction stops to test.

3.7.5 Adverse Event

3.7.5.1 the Severity of adverse events

Moderate: subject is difficult to endure, and needs specially treated, has a direct impact to the recovery of subject's state of an illness.Severe: jeopardize Subject's life can disable or even lethal, and rescue immediately is needed to handle.

3.7.5.2 the record of adverse events

3.7.5.3 the first aid process of adverse events

3.7.6 terminating to test ahead of time

The control of 3.8 mass and quality assurance

3.8.1 the analysis of On Affecting Factors In The Study

3.8.1.1 selective bias

To avoid selective bias, most effective measure is selection random controls design scheme, especially by research object It is layered and is randomly assigned to can fully ensure that the other harmony of study group, with good comparativity into group；It thus can be with It avoids researcher for certain subjective wishes, and at will determines the grouping of subject or receive certain test measure, to avoid Lead to certain subjective desired result.This research uses random controls design scheme, is to avoid selective bias is most effective from arranging It applies.Random device uses table of random number, and hiding is envelope method.

3.8.1.2 bias is measured

When carrying out measuring observation to treatment group and control group, what especially known group is treatment group, how group is control group In the case where, measuring observation very likely Different Results can occurs because of subjective reason, so as to cause the difference in judgement It is different, i.e., it is observed under non-blind, is easily deviated.It is one of important method of Bias control that standard is included in stringent limitation. Originally it studies and defines and is explicitly included in and exclusion criteria, research object is made strictly to be limited in a certain specific range, reduce to each other Difference, be conducive to make objective conclusion to observation factor.

3.8.1.3 measurement property bias

It avoids that measurement property bias most efficient method occurs to be exactly blind, because if researcher knows the grouping of subject Situation, then it is possible that the intentional or unintentional improvement situation for tending to treatment group's state of an illness, it is desirable to develop ideal result. This subject study can not accomplish blind patient due to the particularity of moxa-moxibustion, therefore study first and evaluated using blind, be grouped by not knowing The third party of situation carries out therapeutic evaluation, and second is statisticallyd analyze in data feedback and evaluation using blind, to guarantee result of study It is true and reliable.

3.8.2 research training

In order to guarantee to have formulated research approach before going on smoothly for research, this test are carried out, unite to clinical investigators One training, the training on operation to the filling in of table, random method and laryngoscope, Voice acoustics analysis, be familiar with grasping research process and Detailed rules and regulations are embodied, to improve consistency between the inside observation consistency of researcher and observer, guarantee clinical research knot The reliability of opinion.

3.9 statistical method

This applying topic SPSS 20.0 is for statistical analysis to final data.

Group difference comparison is carried out, the normal distribution of measurement data data is indicated with mean ± standard deviation, with median and four Quantile spacing indicates non-normal data.Enumeration data data carry out group difference comparison, metering money using Chi-square Test Expect that normal distribution and the neat data of variance carry out group difference comparison using independent samples t test and variance analysis, further uses LSD is compared two-by-two, Non-Gaussian Distribution or heterogeneity of variance data, carries out group difference comparison using non-parametric test.P < 0.05 indicates there is significant difference, and P < 0.01 indicates there is extremely significant sex differernce.

3.10 Technology Roadmap

See Fig. 3

4 results of study

Comparison of therapeutic between group after the treatment 3 weeks of 1 two groups of table

From table 1 and Fig. 4: after treatment end, test group have 17 it is effective, 5 are effective, and have 2 in vain, curative effect Be 91.7%, control group have 15 it is effective, 2 be it is effective, invalid has 2, curative effect 89.5%

Symptom compares between two groups after the treatment of table 23 weeks

From table 2: treatment 3 weeks after two groups persistently hawk and foreign body sensation in the throat on have improvement earlier above, test group exists Also there is improvement in abundant expectoration, nasal mucus refluence and heartburn, pectoralgia, stomachache symptom, only exists in SAS scoring when carrying out two comparison among groups Difference (P < 0.05) has statistical significance, illustrates after treatment end that test group is substantially better than pair in terms of improving anxiety symptom According to group.

Safety: in the entire research process of Chinese medicine group, there is adverse reaction in no patient.In the whole of lansoprazole tablet group In a research process, the adverse events for having 1 patient nausea occur, retch, symptom does not occur again after being discontinued.

Conclusion: soothing liver and harmonizing stomach granule therapy Laryngopharyngeal reflux disease (syndrome of incoordination between liver and stomach) of the present invention has preferable clinical efficacy. It is suitable with Western medicine proton pump inhibitor that Laryngopharyngeal reflux disease (syndrome of incoordination between liver and stomach) general curative effect is treated in soothing liver and harmonizing stomach ruling by law, but pair is made With smaller, there is good potential applicability in clinical practice.

Claims

1. a kind of Chinese medicine composition for treating liver-stomach disharmony or/and pharyngeal discomfort, it is characterised in that: it is matched by following weight The bulk pharmaceutical chemicals of ratio are prepared:

It is 7-13 parts of radix bupleuri, 7-13 parts of rhizoma cyperi, 7-13 parts of dried orange peel, 7-13 parts of rhizoma pinellinae praeparata, 7-13 parts of Cortex Magnoliae Officinalis, 7-13 parts of perilla leaf, yellow Even 4.2-7.8 parts, 7-13 parts of myrobalan, 7-13 parts of blood clam, 10.5-19.5 parts of Radix Codonopsis, 7-13 parts of radix paeoniae rubra, 3.5-6.5 parts of Radix Glycyrrhizae.

2. Chinese medicine composition according to claim 1, it is characterised in that: it is the bulk pharmaceutical chemicals preparation by following weight proportion It forms:

10 parts of radix bupleuri, 10 parts of rhizoma cyperi, 10 parts of dried orange peel, 10 parts of rhizoma pinellinae praeparata, 10 parts of Cortex Magnoliae Officinalis, 10 parts of perilla leaf, 6 parts of the coptis, myrobalan 10 Part, 10 parts of blood clam, 15 parts of Radix Codonopsis, 10 parts of radix paeoniae rubra, 5 parts of Radix Glycyrrhizae.

3. Chinese medicine composition according to claim 1 or 2, it is characterised in that: it is the medicinal powder or bulk pharmaceutical chemicals by bulk pharmaceutical chemicals Water or extractive with organic solvent be active constituent, in addition the preparation that pharmaceutically acceptable auxiliary material is prepared.

4. described in any item Chinese medicine compositions according to claim 1~3, it is characterised in that: the preparation is oral preparation.

5. Chinese medicine composition according to claim 4, it is characterised in that: the oral preparation is powder, paste, particle Agent, tablet, capsule, oral solution or dripping pill, preferably granule.

6. the preparation method of any one of Claims 1 to 5 Chinese medicine composition, it is characterised in that: it the following steps are included:

(1) bulk pharmaceutical chemicals are weighed according to proportion described in claim 1；

(2) bulk pharmaceutical chemicals grind water or organic solvent extracting solution for powder or bulk pharmaceutical chemicals, and pharmaceutically common auxiliary material or auxiliary is added Property ingredient to get.

7. the described in any item Chinese medicine compositions of claim 1~6 are in the drug for preparing dispersing stagnated hepatoqi and/or normalizing the stomach by guiding QI downward Purposes.

8. the described in any item Chinese medicine compositions of claim 1~6 are in preparation treatment pectoralgia, heartburn and/or stomachache drug Purposes.

9. purposes of the described in any item Chinese medicine compositions of claim 1~6 in the drug of preparation treatment pharyngeal discomfort.

10. purposes according to claim 9, it is characterised in that: the pharyngeal discomfort be persistently hawk, foreign body in pharynx sense, Abundant expectoration and/or nasal mucus are flow backwards.